Task-induced brain activity patterns in type 2 diabetes: a potential biomarker for cognitive decline
- Thomas J. Marder1,*,
- Veronica L. Flores1,2,*,
- Nicolas R. Bolo3,4,
- Wouter S. Hoogenboom1,5,6,
- Donald C. Simonson4,7,
- Alan M. Jacobson1,4,8,
- Sarah E. Foote1,9,
- Martha E. Shenton4,5,10,
- Reisa A. Sperling4,11,12,13 and
- Gail Musen1,4,†
- 1Clinical, Behavioral, and Outcomes Research, Joslin Diabetes Center, Boston, MA, USA.
- 2Department of Psychology, Brandeis University, Waltham, MA, USA.
- 3Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- 4Harvard Medical School, Boston, MA, USA.
- 5Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA.
- 6Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA
- 7Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA.
- 8Research Institute, Winthrop-University Hospital, Mineola, NY, USA.
- 9Tulane University School of Medicine, Tulane University, New Orleans, LA, USA.
- 10Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA, USA.
- 11Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
- 12Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA.
- 13Athinioula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
- †Corresponding author: Gail Musen, E-mail:
Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network, which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional MRI abnormalities are evident during task performance, including impaired deactivation of the default mode network and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain activity patterns during encoding and recognition tasks. Compared to control participants, we observed both reduced 1) activation of the dorsolateral prefrontal cortex during encoding and 2) deactivation of the default mode network during recognition in type 2 diabetic patients, despite normal cognition. During recognition, activation in several task-relevant regions, including the dorsolateral prefrontal cortex and default mode network regions, was positively correlated with HbA1c and insulin resistance, suggesting that these important markers of glucose metabolism impact the brain’s response to a cognitive challenge. Plasma glucose ≥11 mmol/l was associated with impaired deactivation of the default mode network, suggesting that acute hyperglycemia contributes to brain abnormalities. Since elderly type 2 diabetic patients often demonstrate cognitive impairments, it is possible that these task-induced brain activity patterns observed in middle age may signal impending cognitive decline.
* Thomas J. Marder and Veronica L. Flores contributed equally to this manuscript
- Received November 21, 2013.
- Accepted March 28, 2014.
- © 2014 by the American Diabetes Association.
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